An inherited deficiency of alpha 1-antitrypsin (A1AT) in human serum is associated with pulmonary emphysema and liver cirrhosis. The objective of the proposed project is to elucidate the molecular abnormalities of the variant A1ATs and the mechanism of synthesis and regulation of A1AT level in vivo. The project consists of the following studies: 1) Isolation and chemical characterization (including amino acid substitutions) of variant A1ATs; 2) Determination of the nature of immunologically cross-reactive material accumulated in livers of Pi-ZZ variant subjects; 3) Investigation into the mechanism of synthesis, degradation, accumulation and release of A1AT. BIBLIOGRAPHIC REFERENCE: Akira Yoshida, Jack Lieberman, Laima Gaidulis, Carol Ewing: Molecular Abnormality of Human Alpha 1-Anti-Trypsin Variant (Pi-ZZ) Associated with Plasma Activity Deficiency. Proc. Natl. Acad Sci., U.S.A., 73, 1324-1328 (1976).